This application seeks renewed CCSG funding for the University of Virginia (UVA) Cancer Center, a matrix cancer center that brings together 132 Members from 23 Departments in the Schools of Medicine, Nursing, and Engineering, and in the College of Arts and Sciences. The UVA Cancer Center receives $19.85M from NCI, $48.62M from other peer-reviewed sources, and $8.72M from non-peer-reviewed sources, for a total of $77.19M in overall funding. Through faculty recruitment, re-organization, and robust infrastructure development, the UVA Cancer Center has continued to build on its exceptional basic-science foundations and has greatly enhanced its ability to accelerate clinical and translational cancer-focused research. Twenty-six new faculties have been recruited, including thirteen clinical investigators and/or physician-scientists and eight bioengineers, computational biologists, and/or molecular geneticists. To enhance trans-disciplinary and translational research and cancer focus, programs were consolidated so that all have basic science Members integrated with disease-focused and clinical or translational investigators. The Cancer Center has five Programs; Cancer Cell Signaling (SIG), Chemical and Structural Biology (CSB), Molecular Genetics and Epigenetics (GEN), Women's Oncology (WON), and Immunology/immunotherapy (IMM). The number of Full Members has been reduced by 30% and an Associate Member category has been created for investigators whose potential for peer-reviewed, cancer-focused research has yet to be actualized. This application requests support for eight Shared Resources: Advanced Microscopy, Biomolecular Analysis, Biorepository and Tissue Research, Flow Cytometry, Gene Targeting and Transgenic, Preclinical Tumor Analysis and Imaging, Biostatistics, and the Office for Clinical Research. A completely transformed infrastructure for translational and clinical research facilitates investigations using human tissues and the implementation of clinical trials. Major additions in research and clinical facilities strongly enhance the Cancer Center's ability to carry out its mission: New laboratory space covering 25,000 ft2houses IMM and WON Members, and a new cancer outpatient clinical building covering 151,000 ft2 will open in April 2011. Substantial activities have been initiated to reach underserved populations in minority groups and in Appalachia. This renewal application describes continued excellence in basic cancer research, enhanced cancer focus, and greatly strengthened clinical research leadership and infrastructure.